RESUMO
In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess axon collaterals within the globus pallidus (GPe) (bridging collaterals), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches in mice to dissect the roles of dSPN GPe collaterals in motor function. We find that dSPNs projecting to the SNr send synchronous motor-related information to the GPe via axon collaterals. Inhibition of native activity in dSPN GPe terminals impairs motor activity and function via regulation of Npas1 neurons. We propose a model by which dSPN GPe axon collaterals (striatopallidal Go pathway) act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 neurons.
Assuntos
Axônios , Neurônios , Camundongos , Animais , Neurônios/metabolismo , Axônios/metabolismo , Globo Pálido/fisiologia , Corpo Estriado/metabolismo , Gânglios da Base/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismoRESUMO
After repeatedly failing to get out of a stressful, uncontrollable environment, mice switch from escape behavior to inactivity. In this issue of Neuron, Li et al. identify a circuit involving noradrenergic projections from the locus coeruleus to GABAergic projection neurons in the orbitofrontal cortex that participate in this adaptive behavior.
Assuntos
Encéfalo , Locus Cerúleo , Animais , Camundongos , Humanos , Adaptação Psicológica , Etnicidade , Neurônios GABAérgicosRESUMO
In the classical model of the basal ganglia, direct pathway striatal projection neurons (dSPNs) send projections to the substantia nigra (SNr) and entopeduncular nucleus to regulate motor function. Recent studies have re-established that dSPNs also possess "bridging" collaterals within the globus pallidus (GPe), yet the significance of these collaterals for behavior is unknown. Here we use in vivo optical and chemogenetic tools combined with deep learning approaches to dissect the roles of bridging collaterals in motor function. We find that dSPNs projecting to the SNr send synchronous motor-related information to the GPe via axon collaterals. Inhibition of native activity in dSPN GPe terminals impairs motor activity and function via regulation of pallidostriatal Npas1 neurons. We propose a model by which dSPN GPe collaterals ("striatopallidal Go pathway") act in concert with the canonical terminals in the SNr to support motor control by inhibiting Npas1 signals going back to the striatum.
RESUMO
Cholinergic interneurons (CINs) in the striatum respond to salient stimuli with a multiphasic response, including a pause, in neuronal activity. Slice-physiology experiments have shown the importance of dopamine D2 receptors (D2Rs) in regulating CIN pausing, yet the behavioral significance of the CIN pause and its regulation by dopamine in vivo is still unclear. Here, we show that D2R upregulation in CINs of the nucleus accumbens (NAc) lengthens the pause in CIN activity ex vivo and enlarges a stimulus-evoked decrease in acetylcholine (ACh) levels during behavior. This enhanced dip in ACh levels is associated with a selective deficit in the learning to inhibit responding in a Go/No-Go task. Our data demonstrate, therefore, the importance of CIN D2Rs in modulating the CIN response induced by salient stimuli and point to a role of this response in inhibitory learning. This work has important implications for brain disorders with altered striatal dopamine and ACh function, including schizophrenia and attention-deficit hyperactivity disorder (ADHD).
Assuntos
Dopamina , Receptores de Dopamina D2 , Acetilcolina , Colinérgicos , Corpo Estriado , Interneurônios/fisiologia , Núcleo AccumbensAssuntos
Infecções por Coronavirus/epidemiologia , Internato e Residência/organização & administração , Pneumonia Viral/epidemiologia , Psiquiatria/organização & administração , COVID-19 , Infecções por Coronavirus/prevenção & controle , Humanos , Cidade de Nova Iorque , Inovação Organizacional , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Jornada de Trabalho em TurnosRESUMO
Cytoplasmic dynein mediates retrograde transport in axons, but it is unknown how its transport characteristics are regulated to meet acutely changing demands. We find that stimulus-induced retrograde transport of different cargos requires the local synthesis of different dynein cofactors. Nerve growth factor (NGF)-induced transport of large vesicles requires local synthesis of Lis1, while smaller signalling endosomes require both Lis1 and p150Glued. Lis1 synthesis is also triggered by NGF withdrawal and required for the transport of a death signal. Association of Lis1 transcripts with the microtubule plus-end tracking protein APC is required for their translation in response to NGF stimulation but not for their axonal recruitment and translation upon NGF withdrawal. These studies reveal a critical role for local synthesis of dynein cofactors for the transport of specific cargos and identify association with RNA-binding proteins as a mechanism to establish functionally distinct pools of a single transcript species in axons.